Safety, Tolerability, PK, and Efficacy Evaluation of Repeat Ascending Doses of Olipudase Alfa in Pediatric Patients <18 Years of Age With Acid Sphingomyelinase Deficiency (ASCEND-Peds)

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To evaluate the safety and tolerability of olipudase alfa administered intravenously in pediatric patients every 2 weeks for 52 weeks.

Secondary Objective:

To characterize the pharmacokinetic profile and evaluate the pharmacodynamics and exploratory efficacy of olipudase alfa administered intravenously in pediatric patients every 2 weeks for 52 weeks.

Condition or disease

Intervention/treatment

Phase

Sphingomyelin Lipidosis

Drug: Olipudase alfa

Phase 1Phase 2

Detailed Description:

The maximum study duration per patient is approximately 18 months (screening period: up to 60 days; treatment period: 64 weeks; post-treatment period: up to 37 days, not applicable if patient enrolls in a long term extension treatment trial).

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Layout table for eligibility information

Ages Eligible for Study:

up to 17 Years (Child)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion criteria :

The patient and/or patient's parent(s)/legal guardian(s) must provide written informed assent/consent prior to any protocol-related procedures being performed.

The patient is aged 0 to <18 years of age on the date of informed assent/consent.

The patient has documented deficiency of acid sphingomyelinase as measured in peripheral leukocytes, cultured fibroblasts, or lymphocytes.

The patient has a spleen volume ≥5 multiples of normal (MN) measured by magnetic resonance imaging (MRI); patients who have had partial splenectomy will be allowed if the procedure was performed ≥1 year before screening and the residual spleen volume is ≥5 MN.

Female patients of childbearing potential and male patients must be willing to practice true abstinence in line with their preferred and usual lifestyle, or use 2 acceptable effective methods of contraception.

Exclusion criteria:

The patient has received an investigational drug within 30 days before study enrollment.

Any other extenuating circumstance that can significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.

The patient has acute or rapidly progressive neurological abnormalities.

The patients is homozygous for SMPD1 gene mutations R496L, L302P, and fs330 or any combination of these 3 mutations.

The patient has a delay of gross motor skills.

The patient has had a major organ transplant (eg, bone marrow, liver).

The patient requires use of invasive ventilatory support.

The patient requires use of noninvasive ventilatory support while awake and for >12 hours a day.

The patient, in the investigator's opinion, is unable to adhere to the requirements of the study.

The patient has a platelet count <60 × 10^3/µL (based on the average of 2 screening samples obtained up to 24 hours apart).

The patient has alanine aminotransferase or aspartate aminotransferase >250 IU/L or total bilirubin >1.5 mg/dL.

The patient has an international normalized ratio (INR) >1.5

The patient is unwilling or unable to abstain from ingesting alcohol the day before through 3 days after each infusion of olipudase alfa during the treatment period. Measuring alcohol concentration in blood is not required.

The patient is scheduled during the study for in-patient hospitalization including elective surgery.